Hydrochloric Acid → Ethyl 4-[5-chloro-2-(2,3-difluoro-6-methoxybenzyloxy)-4-nitro-phenyl]butyrate

HRID 1513015Notes

Reaction equation

HRID 1513015 reaction equation
Br[C:2]1[C:7]([O:8][CH2:9][C:10]2[C:15]([O:16][CH3:17])=[CH:14][CH:13]=[C:12]([F:18])[C:11]=2[F:19])=[CH:6][C:5]([N+:20]([O-:22])=[O:21])=[C:4]([Cl:23])[CH:3]=1.[Br-].[CH2:25]([O:27][C:28](=[O:33])[CH2:29][CH2:30][CH2:31][Zn+])[CH3:26].Cl>O1CCCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:23][C:4]1[C:5]([N+:20]([O-:22])=[O:21])=[CH:6][C:7]([O:8][CH2:9][C:10]2[C:15]([O:16][CH3:17])=[CH:14][CH:13]=[C:12]([F:18])[C:11]=2[F:19])=[C:2]([CH2:31][CH2:30][CH2:29][C:28]([O:27][CH2:25][CH3:26])=[O:33])[CH:3]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 685153834-Bromo-2-chloro-5-(2,3-difluoro-6-methoxybenzyloxy)-1-nitrobenzeneHCID 178471550HCID 178471550, compound

Product 1

HCID 68511113Ethyl 4-[5-chloro-2-(2,3-difluoro-6-methoxybenzyloxy)-4-nitro-phenyl]butyrate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 4-bromo-2-chloro-5-(2,3-difluoro-6-methoxybenzyloxy)-1-nitrobenzene (2.04 g) in tetrahydrofuran (10 mL) were added 4-ethoxy-4-oxobutylzinc bromide (0.5 mol/L tetrahydrofuran solution, 12 mL) and tetrakis(triphenylphosphine)palladium(0) (0.2 g), and the mixture was stirred at room temperature under an argon atmosphere overnight. The reaction mixture was poured into 1 mol/L hydrochloric acid, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=4/1−3/2) to give ethyl 4-[5-chloro-2-(2,3-difluoro-6-methoxybenzyloxy)-4-nitro-phenyl]butyrate (0.72 g). This material was dissolved in tetrahydrofuran (5 mL). To the solution were added methanol (5 mL) and nickel(II) bromide (11 mg). To the mixture was added sodium borohydride (0.12 g) under ice-cooling, and the mixture was stirred at the same temperature for 30 minutes, and then stirred at room temperature for 30 minutes. The reaction mixture was poured into a saturated aqueous sodium hydrogen carbonate solution, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=4/1−3/2) to give the title compound (0.41 g).

Workup

  1. extractionthe resulting mixture was extracted with ethyl acetate
  2. washThe extract was washed with water and brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was removed under reduced pressure
  5. customthe residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=4/1−3/2)

Sources & evidence

ORD record
ord-d4bddb10a63f4c999756da39ce46ebb6
Source dataset
uspto-grants-2012_07
Patent number
US08217069B2

Reaction notes

Loading…